陶氏病
蓝斑
突变体
睡眠(系统调用)
神经科学
突变
睡眠剥夺
内分泌学
生物
内科学
昼夜节律
医学
遗传学
神经退行性变
基因
中枢神经系统
疾病
计算机科学
操作系统
作者
Qing Dong,Louis J. Ptáček,Ying‐Hui Fu
标识
DOI:10.1073/pnas.2221686120
摘要
Sleep is essential for our well-being, and chronic sleep deprivation has unfavorable health consequences. We recently demonstrated that two familial natural short sleep (FNSS) mutations, DEC2-P384R and Npsr1-Y206H , are strong genetic modifiers of tauopathy in PS19 mice, a model of tauopathy. To gain more insight into how FNSS variants modify the tau phenotype, we tested the effect of another FNSS gene variant, Adrb1-A187V , by crossing mice with this mutation onto the PS19 background. We found that the Adrb1-A187V mutation helped restore rapid eye movement (REM) sleep and alleviated tau aggregation in a sleep–wake center, the locus coeruleus (LC), in PS19 mice. We found that ADRB1 + neurons in the central amygdala (CeA) sent projections to the LC, and stimulating CeA ADRB1+ neuron activity increased REM sleep. Furthermore, the mutant Adrb1 attenuated tau spreading from the CeA to the LC. Our findings suggest that the Adrb1-A187V mutation protects against tauopathy by both mitigating tau accumulation and attenuating tau spreading.
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